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Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

Review Article

Acquired overview
KH Mohan




Department of Dermatology, Kasturba Medical College, Manipal

Abstract Acquired hyperpigmentation is always difficult to diagnose and more difficult to treat
satisfactorily. There are many conditions which need to be considered before making a diagnosis of acquired macular hyperpigmentation like erythema dyschromicum perstans, lichen planus pigmentosus, macular amyloidosis, tar and frictional melanosis, post-inflammatory hyperpigmentation, Berloque dermatitis, Riehls melanosis and drugs and chemicals. Key words Acquired hyperpigmentation, Berloque dermatitis, Riehls melanosis, erythema dyschromicum perstans

Introduction Hyperpigmentation in general is due to, increased melanin production by existing melanocytes or from increased proliferation of active melanocytes. Hyperpigmentary skin disorders are defined as increased pigmentation of the skin and mucous membranes to the extent that the patient concerned seeks medical advice. These skin disorders may be classified as epidermal and dermal hyperpigmentaion, depending on the location of the pigments. Epidermal hyperpigmentation is because of melanin pigmentation and has a brownish hue. Dermal pigmentation is called ceruloderma or blue hyperpigmentation which may either be due to melanin or due to non-melanin pigments. Differential diagnosis of acquired

hyperpigmented macules is endless. The most common dermatological causes of acquired hyperpigmented macules in clinical practice are, (Table 1) Erythema dyschromicum perstans Lichen planus pigmentosus Macular amyloidosis Friction melanosis Tar melanosis Berloque dermatitis Riehls melanosis Idiopathic eruptive macular pigmentation 9. Post-inflammatory hyperpigmentation 10. Hyperpigmentation due to drugs and heavy metals Erythema dyscromicum perstans (EDP) Synonyms Ashy dermatosis of Ramirez, dermatosis cenicientos, erythema chronicum, figuratum melanodermicum It is an idiopathic, acquired, generalized, macular ashen-grey-blue hypermelanosis which 1. 2. 3. 4. 5. 6. 7. 8.

Address for correspondence Dr. KH Mohan , Assistant Professor Department of Dermatology Kasturba Medical College Manipal- 576104 Udupi Dist, Karnataka,India Mobile 09448563440 E-mail:


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

Table 1 Differentiating above conditions Condition Age Sex Etiology Erythema Any age Both Unknown. dyschromicu F>M ?Ammonium nitrate, n perstans whip worm, contrast media. Lichen Any age Both Unknown. ? HBV, planus F>M HCV.T-Lymphocytic pigmentosus abnormality

Clinical features Ash-coloured, polycyclic macules with elevated borders (piece of string) over trunk, arms, face Discrete dark brown macules over trunk, extensor aspect of arms with pruritus Pruritic, dusky brown or grayish pigmented macules in a rippled pattern over upper back, arms, legs Pigmented reticulated macules over clavicle, knees, elbows, ribs

Macular amyloidosis



Constant rubbing with nylon brush or towel

Friction melanosis

Any age


Chronic constant friction, pressure or irritation by nylon and cotton towels, sponges, brushes Exposure to coal tar, mineral oils and hydrocarbons

Tar melanosis



Berloque dermatitis


Both F>M

Exposure to bergapten, or 5-methoxypsoralen, is the photoactive component of bergamot oil from the bergamot lime (C bergamia), which is a popular ingredient in perfumes and fragrances. Exposure to formaldehyde, brilliant lake red R, musk ambrette, aniline dyes.

Riehls melanosis

Middle age


Idiopathic eruptive macular pigmentation



Hormonal factors may play a role as the condition is seen in the peripubertal age group.

Asymptomatic small bluish-grey hyperpigmented macules which often merge with each other to form large confluent areas involving face, trunk and extremities Brown hyperpigmentation with or without preceding erythema is seen in a droplike or pendantlike configuration. Seen over the sides of the neck in adult females, although it may be seen in any part of the body where perfume was applied followed by sun-exposure. Diffuse or patchy brown pigmentation on the cheeks and the forehead seen. It is more intense on the forehead and the temples, and severe cases may look black, purple, or blueblack. Aymptomatic pigmented macules that involve the face, trunk and proximal extrmities. These occur in crops and gradually resolve over months to years without any scarring and residual pigmentation

Histopathology Non-specific. Mild basal cell degeneration with perivascular mononuclear cell infiltrate Atrophic epidermis, vacuolar degeneration of basal cell layer with lichenoid infiltrate of upper dermis Globular, amorphous amyloid deposits seen in dermal papillae. Congo red stain positive. Flattened epidermis with isolated necrosis of keratinocytes and areas of the cleavage of the dermoepidermal junction leading melanin incontinence Follicular hyperkeratosis, reduced basal cell pigmentation, pigmentary incontinence and perivascular lymphocytic infiltration The epidermal changes consist of keratinocyte necrosis, intercellular and intracellular edema, and intraepidermal blisters. Dermis shows mild perivascular infiltrate.

Interface changes occur with liquefactive basal cell degeneration. A moderate lymphohistiocytic infiltrate is present in the upper dermis, mainly in a perivascular distribution. Epidermal hypermelanosis with increased melanin in the basal layer of the epidermis and variable dermal inflammation and melanophages in the dermis


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

Condition Postinflamma tory pigmentation

Age Any age

sex F=M

Etiology Allergic reactions, infections, trauma, and phototoxic eruptions. Acne excorie, lichen planus, systemic lupus erythematosus, chronic dermatitis, and cutaneous T-cell lymphoma, especially erythrodermic variants

Pigmentation due to drugs/Heavy metals

Any age


Amiodarone, antimalarials, bleomycin, busulfan, cyclophosphamide, dactinomycin, daunorubicin and 5 FU, Minocycline Chlorpromazine, Bismuth, gold, mercury, silver

Clinical features The distribution of the hypermelanotic lesions depends on the location of the original inflammatory dermatosis. The color of the lesions ranges from light brown to black, with a lighter brown appearance if the pigment is within the epidermis and a darker gray appearance if lesions contain dermal melanin Amiodarone - slate-grey, Antimalarials - yellowbrown, Bleomycin - flagellate hyperpigmention, Minocycline - grayish discolouration, Gold blue-grey deposits around eyes, Silver - diffuse slate-grey discolouration of sunexposed areas.

Cont.. Histopathology Epidermal PIH involves increased melanin pigment in the basal cell layer of the epidermis. Dermal PIH involves the upper dermis, with pigment incontinence due to increased numbers of melanophages in the papillary dermis.

Increased melanin in the epidermis (tends to be more brown, hence hyperpigmented), melanin in the epidermis and high dermis (mostly brown with hints of grey or blue), increased melanin in the dermis (tends to be more greyish or blue), and dermal deposition of the drug or metabolite (usually slate or bluish grey).

occurs in otherwise healthy individuals. Lesions begin as erythematous macules, which later develop a slate-grey or ashen hue (Figure 1). Usually the lesions are flat but active lesions may have a slightly raised, erythematous border like a thin piece of string. Lesions are usually numerous and may vary in size from few millimeters to many centimeters and have a tendency to coalesce and cover extensive areas of trunk, limbs and face. They have not been found on the soles, palms, nails or the mucous membrane. They are usually asymptomatic. The etiology of EDP is unknown and is not associated with any internal condition, although isolated reports of ammonium nitrate ingestion1,9,10 and whipworm (Trichuris trichiura) infestation2 have been suggested to be the cause.

Histopathology In the early active stage, many basal cells and some squamous cells in the lower epidermis show vacuolization of their cytoplasm. This leads to liquefaction degeneration. The upper dermis shows a mild to moderate perivascular infiltrate. This infiltrate consists of lymphocytes and histiocytes intermingled with melanophages. Occasional colloid bodies, resembling those seen in lichen planus, may be present. Damage to basal layer, resulting in formation of colloid bodies and pigmenting incontinence, suggests a possible relationship of EDP to lichen planus pigmentosus.15,3 It is true that lichen planus pigmentosus has a more pronounced lichenoid infiltrate and its lesions have a greater predilection to be located in the exposed areas but the occasionally described coexistence of


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

Figure 1 Slate-grey coloured macules of erythema dyschromicum perstans.

Figure 2 Brownish-black macules of lichen planus pigmentosus.

Figure 3 Bluish-grey hyperpigmented macules over face. Figure 4 Brownish macules over face.

Figure 5 Pigmented macules of idiopathic eruptive macular pigmentation.

Figure 6 Hyperpigmented macules over trunk due to psoriasis.


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

the two conditions suggests that they are related. Treatment Many therapeutic options are available, but few have been effective, except for clofazimine. Clofazimine is a lipophilic rhimophenazine dye with both antimicrobial and anti-inflammatory properties originally developed to treat tuberculosis. Although its mechanism of action is unclear, it seems to exert its main effect upon neutrophils and monocytes in a variety of ways, such as stimulating phagocytosis and release of lysosomal enzymes. Clofazimine is administered orally, with improved bioavailability when taken with food. It concentrates in lipid-rich tissues, including the reticuloendothelial system, the intestine, the breasts, and the liver. Its half-life is 70 days. Isoniazid increases its serum levels and enhances its urinary excretion. Its most common adverse effects are in the skin, the gut, and the eye. It gives a temporary orange discoloration of the skin and the eye (ie, cornea, conjunctivae); it also may produce ichthyosis. Its most serious adverse effect is crystal deposition in the gut that produces a potentially fatal enteropathy. This rare complication is associated with months of high-dose (>100 mg/day) therapy. Nausea and diarrhea are more common. Splenic infarction and eosinophilic enteritis are also rare adverse effects. Many other therapeutic modalities have been attempted, none with satisfactory results. These include dapsone, ultraviolet exposure, ultraviolet avoidance, antibiotics, antihistamines, griseofulvin, chemical peels, antibiotics, corticosteroids, vitamins, isoniazid, chloroquine, and psychotherapy.

Lichen planus pigmentosus (LPP) Synonym Invisible pigmented lichen planus. It was described in 1956 by Shima et al. Lichen planus pigmentosus is characterized by discrete dark brown macules with non-characteristic distribution that predominates in exposed areas and flexor folds.3,14,11 It commonly occurs on the trunk and extensor aspect of arms. Its evolution is characterized by exacerbations and remissions. In some cases there may be associated pruritus. The lesions characteristically spare the muocus membranes, palms and soles. In a study by Kanwar, in 124 Indian patients with lichen planus pigmentosus, the face and neck were the commonest sites affected with pigmentation varying from slate grey to brownish-black. The pattern of pigmentation was mostly diffuse (77.4%) [Figure 2], followed by reticular (9.7%), blotchy (7.3%) and perifollicular (5.6%). Lichen planus was noted in 19 patients with typical histopathological changes of the disorder. The histopathologic picture of LPP shows an atrophic epidermis with vacuolar degeneration of the basal cell layer. In the dermis, a scarce lymphohistiocytic or lichenoid infiltrate and pigmentary incontinence with melanophages can be found. Treatment It has a prolonged course and resistant treatment. Potent and moderately potent steroids were tried. It is resistant to tacrolimus also. Vitamin A has been tried successfully in the treatment of LPP.18 Macular amyloidosis It is a form of primary localized cutaneous amyloidosis. The main feature of primary cutaneous amyloidosis is the accumulation of


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

amyloid in previous apparently normal skin without any deposits in the internal organs. Macular amyloidosis (MA) is the most subtle of the cutaneous amyloidosis. The original description of this entity was made by Palitz and Peck in 1952. It is more common among central and south Americans, middle easterns and Asians who have dark skin. It is rare among European and North American races. Amyloid deposits in MA bind to antikeratin antibodies. These deposits contain sulfhydryl groups pointing to altered keratin as a source for these deposits. Apaydin et al. found no differences in staining characteristics of cytokeratins between MA. Interestingly, in their study, all the cytokeratins detected in amyloid deposits were of basic type (type II). This may be because, in amyloidogenesis, acidic cytokeratins such as cytokeratin 14 are degraded faster than basic types. The exact origin of amyloid deposits in MA has not been determined. Two theories have been proposed to explain the origin of the amyloid deposits. These theories are not mutually exclusive, and both could be possible. Fibrillar body theory This theory proposed by Hashimoto suggests that the necrotic epidermal cells (colloid bodies) are transformed into amyloid by dermal macrophages and fibroblasts by a process called filamentous degeneration. The absence of amyloid deposits in other dermatoses with colloid bodies (e.g. lichen planus) is explained by the brisk inflammatory reaction clearing them promptly in lichen planus, while the lack of inflammatory cells leads to the formation of amyloid deposits in MA. This theory does not explain how the alpha type of keratin tertiary

structure is degraded and converted into the beta-pleated sheet configuration of amyloid. Secretory theory This theory proposed by Yamagihara et al. suggests that the amyloid in MA is secreted by disrupted basal cells and is assembled at the dermoepidermal junction (DEJ). Clinical features The lesions consist of macular hyperpigmented areas predominantly on the upper back (interscapular area), buttocks, chest (over clavicles, on the ribs), breast and extremities (shins and forearms). Lesions appear as grayishbrown macules, 2-3 mm in diameter. A reticulate or rippled pattern of pigmentation is a characteristic diagnostic feature in many cases of macular amyloidosis. Macules may have mild to moderate pruritus. Sometimes pruritus may be absent. The condition usually presents in early adult life and persists for many years. Both sexes may be equally affected. Macular and lichen amyloidosis frequently coexit giving evidence to the concept of biphasic amyloidosis. Histpathology shows amyloid deposited in and confined to the papillary dermis and does not extend beyond the subpapillary plexus. When routine stains are used, amyloid has amorphous, glassy appearance. Amyloid exhibit green birefringence with Congo red when viewed under polarizing microscope. This is because of perpendicular arrangement of fibrillary deposits. Fluorescent stains like thioflaine-T can also be used to demonstrate amyloid. Other stains used are methyl violet, cresyl violet,2,13 periodic acidsciff (PAS), van Giesons, pagoda red, RIT scarlet No 5, RIT cardinal red No 9 and dylon.


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

Direct immunofluorescence usually reveals focal Ig G, Ig M and C3. Treatment Sedating antihistamines have been found to be moderately effective. Topical dimethyl sulfoxide (DMSO), a chemical solvent, and intralesional steroids are beneficial if combined with other modalities. DMSO has been used with moderate success, but failures have also been reported. Pandhi et al. reported a lack of effect with DMSO treatment for cutaneous amyloidosis. Treatment with ultraviolet B (UV-B) light can provide symptomatic relief. Friction melanosis It is characterized by hyperpigmentation over bony prominences, secondary to the friction associated during showering.4 It may be due to prolonged mechanical friction pressure or chronic irritation. The tools used for causing friction may be nylon towels, sponges, cotton towels, brushes and back scratchers etc. Race seems to be important because it is common disorder among Japanese and Latin Americans who share similar skin color. Clinical examination reveals well-circumscribed reticulated macules. It is localized in the clavicular zones, trunk (mainly over scapular areas), neck, knees, elbows, ribs and extremities. Lesions are usually asymptomatic and they have a chronic indolent course. Though the pathogenesis of this condition remains unclear, it seems likely that it is due to prolonged mechanical friction, pressure and chronic irritation as they appear over osseous prominences. Another factor of this pigmentation is contact dermatitis to components of nylon such as phenol, formalin, mercuric chloride, phenylmercuric acetate and formaldehyde.

Histologically, there is flattened epidermis with isolated necrosis of keratinocytes and micrscopic areas of the cleavage of the dermo-epidermal junction which lead to incontinence of pigment in the form of free melanin in the dermis or within the dermal macrophages. Treatment Removal of the cause is the main treatment. Patients should avoid rubbing the skin with nylon towels, sponges, cotton towels, brushes and back scratchers etc. Tar melanosis Tar melanosis has also been called occupational melanosis, melanodermatitis xerotica or toxic melanodermatitis. This is commonly encountered among workers with tar, coal tar products, mineral oils and other hydrocarbons. Substances in coal tar with phototoxic properties are anthracene, benzpyrine, acridine, phenanthrene, pyridine etc. Tar melanosis is characterized by the development of asymptomatic small bluish-grey hyperpigmented macules which often merge with each other to form large confluent areas involving face (Figure 3), trunk and extremities and lesions of the forearm and legs tend to be perifollicular. In early stages there is erythema, edema, vesiculation and pruritus. Later, cutaneous hyperpigmentation in a reticulate pattern gradually develops with variable degree of atrophy, telangiectasia, scaling and follicular keratosis. Histological examination reveals follicular hyperkeratosis, reduced basal cell pigmentation, pigmentary incontinence and perivascular lymphocytic infiltration.2


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Treatment Avoidance of the exposure to tar and tar containing products helps in the improvement of pigmentation. Any pigment reducing substances like hydroquinone, glycolic acid, azaelic acid or kojic acid can be used. Berloque dermatitis Synonym Photocontact dermatitis Phototoxicity or photoirritation is a chemically induced nonimmunologic acute skin irritation requiring light (usually within the UVA spectrum, ie, 320-400 nm). The skin response resembles exaggerated sunburn and does not require prior sensitization; it can be caused by a single simultaneous exposure to the chemical and light source. The photoactive chemical may enter the skin via topical administration, or via ingestion, inhalation, or parenteral administration. The reaction can be evoked in all subjects as long as the concentration of the chemical and the dose of light are sufficient. In the case of berloque dermatitis, the phototoxic reaction is induced by the effect of long-wave ultraviolet (UVA) radiation on bergapten, or 5methoxypsoralens, a furocoumarin now known to be the only photoactive component of bergamot oil. The bergapten-UVA radiation combination induces an intensification of melanogenesis and a corresponding increase in the number of functional melanocytes, which are more dendritic and dopa-positive. The distribution of melanosomes in keratinocyte changes from the aggregate to nonaggregate form. Hyperpigmentation is rarely preceded by erythema, pruritus or a severe phototoxic reaction. There is rarely any inflammatory phase. Following light exposure, there will be

development of deep brown cutaneous pigmentation over the primary sites of application of the perfume and along the course of its subsequent trickling. Because the perfume is often applied to the chest, the ensuing photodermatitis which resembles a pendent, was referred to as necklace dermatitis. Treatment The primary aim of the therapeutic regime is discontinuation of the offending substance. If berloque dermatitis is the putative diagnosis, all bergamot oil-containing perfumes should be avoided. Any perfumes that are worn should be worn on covered-up areas, not on areas of sun exposure. If the patient presents in the acute phase and is in considerable discomfort, wet compresses may be helpful in relieving the discomfort. Simple analgesia may be given if the patient is in pain. For secondary hyperpigmentation, the natural course of the dermatitis is spontaneous resolution after several months, but some lesions may persist much longer. The most important step is to minimize exposure to the sun. This may be done by avoiding strong sunlight whenever possible, avoiding the use of sunbeds and using a strong sunscreen (SPF 30 or higher) with activity in both the UVA and UVB spectra. Camouflage also may be used on exposed hyperpigmented areas, for cosmetic reasons. If the pigmentation is persistent, hydroquinone constitutes the mainstay of medical therapy. It usually is given twice a day, at a concentration of about 2%, for several months. At higher concentrations, the patient would be at risk of irritation. Hydroquinone sometimes is administered in conjunction with topical tretinoin (Retin-A). Kligman and Willis devised a concoction known as Kligman's formula,


Journal of Pakistan Association of Dermatologists 2011; 21: 43-54.

consisting of hydroquinone, tretinoin, dexamethasone, ethanol, and propylene glycol, which they found effective in treating hyperpigmentation. A novel therapy for pigmentary disorders is ellagic acid, now commercialized in Japan. Ellagic acid is a naturally existing polyphenol that inhibits tyrosinase activity by chelation of the copper ion at the active center of the enzyme. Riehls Melanosis Riehl melanosis is a nonpruritic pigmentary dermatosis affecting the face. It was first observed in 1917. It is characterized by brownish grey facial pigmentation that is more marked on the temples and the forehead. Riehls melanosis was later noted to occur in people with dark complexions in whom hyperpigmentation with pigment incontinence may be the main sign of contact dermatitis caused by certain allergens. Today, Riehl melanosis is almost synonymous with pigmented contact dermatitis of the face, the most common causes of which are sensitizing chemicals in cosmetics. Clinical feature Riehls melanosis is characterized by reticular, black to brown, violet pigmentation of the face.2 Pigmentation is more intense on the forehead, zygomatic and/ or temporal regions (Figure 4). Pigmentation may extend to the chest, neck and scalp. Various etiological factors have been incriminated for Riehls melanosis. The disease has also been called as war melanosis because of its occurrence during and after both world wars. This was attributed to exposure to tar. The disease was called Pigmented contact dermatitis by Nakayama.5,12 Although the etiology remains unsettled, Riehls melanosis

may be a result of contact sensitivity or photocontact dermatitis related to a chemical, particularly a fragrance, found in cosmetics. Histologically, in the early stages there is liquefaction degeneration of the basal layer of epidermis and a perivascular or band-like dermal infiltrate. There is also pigmentary incontinence. Later, the epidermis appears normal, but many melanophages are present in the upper dermis. Treatment Avoidance of the allergen is necessary when it is identified. UV light may have a role to play; theoretically, some patients may benefit from sun avoidance and sunblocks where photoaggravation is established. No effective treatment/cure of Riehls melanosis has been reported. Idiopathic eruptive macular pigmentation (IEMP) Idiopathic eruptive macular pigmentation (IEMP) is a benign, self-limiting melanosis commoly occurs in children and adolescents. It is characterized by the presence of asymptomatic pigmented macules that involve the face, trunk and proximal extremities (Figure 5).7,16 These occur in crops and gradually resolve over months to years without any scarring and residual pigmentation. The first description was by Degos et al.6 in 1978 in French while in English was by Sanz de Galdeano et al. in 1996. Histopathologically, IEMP is an epidermal hypermelanosis with increased melanin in the basal layer of the epidermis and variable dermal inflammation and melanophages in the dermis. Although these are not specific, biopsy is important to exclude the other conditions, which clinically resemble it. The pathogenesis is not known and it is possible that hormonal factors


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may play a role as the condition is seen in the peripubertal age group. Treatment Active treatment of this asymptomatic condition is unnecessary as it spontaneously resolves within months to years. Post-inflammatory hyperpigmentation Post-inflammatory hyperpigmentation (PIH) is caused by 1 of 2 mechanisms that result in either epidermal melanosis or dermal melanosis. The epidermal inflammatory response (i.e. dermatitis) results in the release and subsequent oxidation of arachidonic acid to prostaglandins, leukotrienes, and other products. These products of inflammation alter the activity of both immune cells and melanocytes. Specifically, these inflammatory products stimulate epidermal melanocytes, causing them to increase the synthesis of melanin and subsequently to increase the transfer of pigment to surrounding keratinocytes. Such increased stimulation and transfer of melanin granules results in epidermal hypermelanosis. On the contrary, dermal melanosis occurs when inflammation disrupts the basal cell layer, causing melanin pigment to be released and subsequently trapped by macrophages in the papillary dermis, also known as pigmentary incontinence PIH can occur with various disease processes that affect the skin. These processes include allergic reactions, infections, trauma, and phototoxic eruptions. Fractional laser photothermolysis occasionally induces PIH. Common inflammatory diseases that result in PIH include acne excorie, lichen planus, psoriasis (Figure 6), systemic lupus erythematosus, chronic dermatitis, and cutaneous T-cell lymphoma, especially erythrodermic variants. Furthermore, lesions of

PIH can darken with exposure to UV light and various chemicals and medications, such as tetracycline, bleomycin, doxorubicin, 5fluorouracil, busulfan, arsenicals, silver, gold, antimalarial drugs, hormones, and clofazimine. Treatment A variety of topical treatments have been used to treat epidermal PIH, with varying degrees of success. These agents include hydroquinone, tretinoin cream, corticosteroids, glycolic acid (GA), and azelaic acid. Topical tretinoin 0.1% has been effective in African Americans. GA peels, in combination with tretinoin and hydroquinone, are an effective treatment of PIH in dark-complexioned individuals. After sufficient improvement of the hyperpigmentation is achieved, a corticosteroid may be applied topically with hydroquinone to promote healing. This combination of various topical therapeutic agents has been shown to be beneficial, especially on the face. Topical azelaic acid, which has been approved for the treatment of acne vulgaris, is useful for postinflammatory hyperpigmentation. Other treatment modalities include use of trichloroacetic acid and gentle cryotherapy with liquid nitrogen. Each method must be used with extreme caution to avoid necrosis or blistering of the treated skin. These 2 methods of treatment should be avoided in dark-skinned patients because of the risk of permanent depigmentation and scarring. Hyperpigmentation due to drugs and heavy metals Mechanisms include increased melanin in the epidermis (tends to be more brown, hence hyperpigmented), melanin in the epidermis and high dermis (mostly brown with tints of grey or blue), increased melanin in the dermis (tends


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Table 2 Morphology of drug induced hyperpigmentation Drug Pattern of pigmentation Amiodarone Slate-gray to violaceous pigmentation of sun exposed areas Antimalarials Yellow-brown to bluish black discolouration of pretibial region, face, oral cavity Bleomycin Flagellate hyperpigmented streaks on the back Busulfan, cyclophosphamide, Diffuse hyperpigmentation dactinomycin, daunorubicin and 5-fluorouracil Minocycline Greyish discolouration of teeth, nails, sclera, oral mucosa. Chlorpromazine Greyish blue discolouration of sun-exposed areas Heavy metals Bismuth Blue-grey discolouration of face, neck and hands Gold Blue-grey deposits around eyes Mercury Slate-grey discolouration of skin folds Silver Diffuse slate-grey discolouration of sun-exposed areas

to be more greyish or blue), and dermal deposition of the drug or metabolite (usually slate or bluish gray). Focal hyperpigmentation frequently follows drug-induced lichen planus (also known as lichenoid drug reactions). Morphological patterns of pigmentation secondary to drugs or heavy metals are shown in Table 2. Treatment The most important factor in the management of drug-induced or heavy metal dyspigmentation involves the identification and discontinuation of the offending drug or heavy metal. Most mucocutaneous pigmentation is reversible and spontaneously resolves with avoidance of the inciting drug. In addition, exposure to sun or UV light may increase pigmentation, especially after sensitization with a photosensitizing medication. Sunscreen use and vigilant avoidance of the sun are helpful to prevent progression or recurrence of pigmentary changes. Finally, topical depigmenting agents and laser treatments (eg, Q-switched alexandrite laser, Qswitched ruby laser) have been reported to improve cases of permanent dyspigmentation.

1. Jablonska S. Ingestion of ammonium nitrate as a possible cause of erythema dyschromicum perstans (ashy dermatosis). Dermatologica 1975; 150; 287-91. Mosher DB, Fitzpatrick TB, Ortonne JP et al. Disorders of pigmentation. In, Dermatology in General Medicine (Fitzpatrick TB, Eisen AZ, Wolff K, et al eds), 4th edn. New York: McGraw-Hill, 1993; 903-995. Memije EV, Waxtein L, Arenas R et al. Ashy dermatosis versus Lichen planus pigmentosus: A controversial matter. Int J Dermatol 1992; 31; 87-8. Domnguez-Soto L, Hojyo-Tomoka MT, Memije EV et al. Pigmentary problems in the Tropics. Dermatol Clin 1994; 12:77784. Nakayama H, Pigmented contact dermatitis. Int J Dermatol 1976; 15; 673. Degos R, Civatte J, Belaich S. Idiopathic eruptive macular pigmentation. Ann Dermatol Venereol 1978; 105; 177-82. Joshi R. Idiopathic eruptive macular pigmentation with papillomatosis: Report of nine cases. Indian J Dermatol Venereol Leprol 2007; 73; 402-5. Granstein RD, Sober A. Drug and heavy metal induced hyperpigmentation. J Am Acad Dermatol 1981; 5; 1-18. Naidorf KF, Cochen SR. Erythema dyschromicum perstans and lichen planus. Arch Dermatol 1982; 118; 683-5.




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10. Stevenson JR, Miura M. Erythem dyschromicum perstans. Arch Dermatol 1966; 94; 196-9. 11. Bhutani LK, Bedi TR, Pandhi RK et al. Lichen planus pigmentosus. Dermatologica 1974; 149; 43-50. 12. Rorsman H. Riehls melanosis. Int J Dermatol 1982; 21: 75-8. 13. Brownstein MH, Hashimoto K. Macular amyloidosis. Arch Dermatol 1972; 106; 507. 14. Bhutani LK. Ashy dermatoses or lichen planus pigmentosus: what is in a name? Arch Dermatol 1986; 122; 133. 15. Berger RS, Hayes TJ, Dixon SL. Erythema dyschromicum perstans and lichen planus:

are they related? J Am Acad Dermatol 1989; 21; 438-2. 16. Jang KA, Choi JH, Sung KS, Moon KC, Koh JK. Idiopathic eruptive macular pigmentation: Report of 10 cases. J Am Acad Dermatol 2001; 44; 351-3. 17. Kanwar AJ, Dogra S, Handa S et al. A study of 124 Indian patients with lichen planus pigmentosus. Clin Exp Dermatol 2003; 28: 481-5. 18. Bhutani LK, George M, Bhate SM. Vitamin A in the treatment of lichen planus pigmentosus. Br J Dermatol 1979; 4: 4735.